Study of Abiraterone Acetate Plus ADT Versus APALUTAMIDE Versus Abiraterone and APALUTAMIDE in Patients With Advanced Prostate Cancer With Non-castrate Testosterone Levels

NCT02867020 | Completed Phase 2

• 1 other identifier: LACOG 0415
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 14

Brief Summary

Evaluation of the activity, safety and patients reported outcome of ADT plus abiraterone, abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or APALUTAMIDE alone in hormone naïve locally advanced or metastatic prostate cancer which ADT was indicated.

Conditions

Prostate Cancer

Keywords

apalutamide; abiraterone; prostate cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients that achieves an undetectable PSA level, defined as ≤ 0.2 ng/mL

  Week 25

Secondary Outcomes (18)

• PSA progression rate

  Week 25

• Comparison of PSA progression rate

  Week 25

• PSA response of 50 and 80%

  Week 25

• Comparison of PSA response of 50 and 80%

  Week 25

• Maximum PSA declines

  Baseline up to week 25 to 52

Study Arms (3)

Abiraterone acetate + Prednisone + ADT (Goserelin)

ACTIVE COMPARATOR

* Abiraterone administered at a single 1000 mg daily oral dose (4 x 250-mg tablets) * Prednisone administered at a 5 mg twice daily oral dose * Goserelin administered as subcutaneous injections of 10.8mg every 3 months

Drug: Apalutamide; Drug: Abiraterone; Drug: ADT

APALUTAMIDE monotherapy

EXPERIMENTAL

o APALUTAMIDE administered at a single 240 mg daily oral dose (4 x 60 mg tablets)

Drug: Apalutamide

Abiraterone acetate + Prednisone + APALUTAMIDE

EXPERIMENTAL

* Abiraterone administered at a single 1000 mg daily oral dose (4 x 250 mg tablets) * Prednisone administered at a 5 mg twice daily oral dose * APALUTAMIDE administered at a single 240 mg daily oral dose (4 x 60 mg tablets)

Drug: Apalutamide; Drug: Abiraterone; Drug: Prednisone

Interventions

Apalutamide DRUG

APALUTAMIDE 240-mg orally once daily (4 x 60-mg tablets) will be administered on a continual basis. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days.

APALUTAMIDE monotherapy; Abiraterone acetate + Prednisone + ADT (Goserelin); Abiraterone acetate + Prednisone + APALUTAMIDE

Abiraterone DRUG

Abiraterone acetate 1,000 mg (four 250 mg tablets) should be taken orally once daily, in combination with oral dose prednisone 5mg twice daily continuously. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days

Abiraterone acetate + Prednisone + ADT (Goserelin); Abiraterone acetate + Prednisone + APALUTAMIDE

ADT DRUG

Dosing of goserelin (dose and frequency of administration) will be consistent with the prescribing information and should only be adjusted if clinically indicated to achieve and maintain subcastrate concentrations of testosterone (50 ng/dL or 1.7 nM).

Also known as: Goserelin

Abiraterone acetate + Prednisone + ADT (Goserelin)

Prednisone DRUG

Subjects will receive prednisone 10mg/day.

Abiraterone acetate + Prednisone + APALUTAMIDE

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate adenocarcinoma;
• Hormone naïve patients with indication to ADT in the following settings:
• Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy): T category T3/4 or node positive
• Biochemical relapse after primary treatment (surgery or radiotherapy): patients in whom primary therapy is not appropriate or feasible with Previously treated with radical surgery and/or radiotherapy, now relapsing with at least one of the criteria: PSA \>= 4 ng/ml and rising with doubling time less than 10 months. or PSA \>= 20 ng/ml or N+ or M+
• Newly diagnosed metastatic disease: Tany Nany M+
• Patient is asymptomatic or moderately symptomatic regarding bone symptoms, i.e., no need for palliative radiation or radionuclide therapy;
• Non-castration level of testosterone \> 230ng/dL (\> 8 nmol/L);
• Baseline level of prostatespecific antigen (PSA) \> 2ng/dL;
• ECOG performance status of 0 to 2;
• Adequate hematologic, hepatic and renal function:
• hemoglobin \> 10 g/dL, neutrophils \> 1.5×109 / L, platelets\> 100×109 / L;
• total bilirubin \< 1.5x upper limit of normal (ULN); alanine (ALT) and aspartate (AST) aminotransferase \< 2.5 x ULN;
• serum creatinine \< 1.5x ULN; potassium \> 3.5 mM;
• No previous cancer (except treated basal-cell skin cancer);
• Written informed consent obtained prior to any study procedure;

You may not qualify if:

• Prostate adenocarcinoma with neuroendocrine differentiation or small cell histology;
• Biochemical recurrence without evidence of clinical or radiological disease;
• Use of hormonal therapy or chemotherapy prior to randomization. Exception is courses of hormone therapy for localised disease must have been completed at least 12 months previously. It can have been given as adjuvant or neoadjuvant therapy.
• Prior radiation therapy for a primary tumour within the 3 months before enrollment or for the treatment of metastases;
• Known or suspected brain or skull metastases or leptomeningeal metastatic disease;
• Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study;
• Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study;
• Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction;
• Current or prior treatment with anti-epileptic medications for the treatment of seizures;
• Impaired cardiac function, including any of the following:
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg);
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease;
• Existing atrial fibrillation with or without pharmacotherapy. Other cardiac arrhythmia requiring pharmacotherapy;
• History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect);
• Specific underlying conditions for oral agents. For example: impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abiraterone or APALUTAMIDE (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (14)

CRIO

Fortaleza, Ceará, Brazil

Location

Clínica AMO

Salvador, Estado de Bahia, Brazil

Location

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Location

Oncologia Rede D'Or S.A.

Rio de Janeiro, Rio de Janeiro, 22281 100, Brazil

Location

Liga Norte Riograndense de Oncologia

Natal, Rio Grande do Norte, Brazil

Location

Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, Brazil

Location

CPO - Pucrs

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Location

Centro de Pesquisa Clínica em Hematologia e Oncologia - CEPHO

Santo André, São Paulo, Brazil

Location

Grupo COI

Rio de Janeiro, Brazil

Location

Beneficiencia Portuguesa de São Paulo/Hospital São José

São Paulo, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

IBCC

São Paulo, Brazil

Location

ICESP

São Paulo, Brazil

Location

Related Publications (23)

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MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; abiraterone; Goserelin; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Fernando Maluf, MD

  Beneficiência Portuguesa de São Paulo

  PRINCIPAL INVESTIGATOR

• Gustavo Werutsky, MD

  Latin American Cooperative Oncology Group

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 15, 2016
• Study Start: October 11, 2017
• Primary Completion: October 9, 2019
• Study Completion: June 30, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-07

Locations

BR (14)